Psychosocial predictors and outcomes of loneliness trajectories from childhood to early adolescence

Using latent class growth analysis, we were interested in investigating how experiences of loneliness emerge in distinct developmental patterns over the course of middle childhood and adolescence (NICHD Study of Early Child Care, N = 832). Second, we examined the role of demographic, mental health, and behavioral variables in association with these discrete patterns of loneliness. Loneliness was measured at 3 time points: age 9, age 11, and age 15. Results indicated five discrete trajectories of loneliness from middle childhood to adolescence. Most children exhibited a stable and low level of loneliness over time. The remaining children were split among moderate increasing, high increasing, decreasing, and chronic loneliness groups. Ethnicity, income, age 7 social skills, age 7 depression, and age 7 aggression were associated with trajectory membership. In addition, the loneliness trajectories predicted self-reports of social skills deficits, depression, aggression, and suicidal ideation at age 15.     

Biopsy‐proven acute cellular rejection as an efficacy endpoint of randomized trials in liver transplantation: a systematic review and critical appraisal

Biopsy‐proven acute cellular rejection (ACR) is the primary efficacy endpoint in most randomized trials evaluating immunosuppression in liver transplantation. However, ACR is not a major cause of graft loss, and a certain grade of immune activation may be even beneficial for long‐term graft acceptance. Validated criteria to select candidates for liver biopsy are lacking, and routine clinical practice relies on liver tests, which are inaccurate markers of ACR. Indeed, both the agreement among clinicians to select candidates for liver biopsy and the correlation between the clinical suspicion of ACR and histological findings are poor. In randomized trials evaluating immunosuppression protocols, this concern grows exponentially due to the open‐label and multicenter nature of most studies. Therefore, biopsy‐proven ACR is a suboptimal efficacy endpoint given its limited impact on prognosis and the heterogeneous diagnosis, which may increase the risk of bias. Chronic rejection and/or graft loss would be more appropriate endpoints, but would certainly require larger studies with prolonged surveillances. An objective method to select candidates for liver biopsy is therefore urgently needed, and only severe episodes of histological ACR should be considered as potentially harmful. Emerging surrogate markers of ACR and antibody‐mediated rejection require further investigation to determine their clinical role.     

Endoscopic ultrasonography-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer: An update

Pancreatic cancer produces disabling abdominal pain, and the pain medical management for pancreatic cancer is often challenging because it mainly relies on the use of narcotics(major opioids). However, opioids often provide suboptimal pain relief, and the use of opioids can lead to patient tolerance and several side effects that considerably reduce the quality of life of pancreatic cancer patients. Endosonography-guided celiac plexus neurolysis(EUS-CPN) is an alternative for pain control in patients with nonsurgical pancreatic cancer; EUS-CPN consists of the injection of alcohol and a local anesthetic into the area of the celiac plexus to achieve chemical ablation of the nerve tissue. EUS-CPN via the transgastric approach is a safer and more accessible technique than the percutaneous approach. We have reviewed most of the studies that evaluate the efficacy of EUSCPN and that have compared the different approaches that have been performed by endosonographers. The efficacy of EUS-CPN varies from 50% to 94% in the different studies, and EUS-CPN has a pain relief duration of 4–8 wk. Several factors are involved in its efficacy, such as the onset of pain, previous use of chemotherapy, presence of metastatic disease, EUS-CPN technique, type of needle or neurolytic agent used, etc. According to this review, injection into the ganglia may be the best technique, and a good visualization of the ganglia is the best predictor for a good EUS-CPN response, although more studies are needed. However, any of the 4 different techniques could be used to perform EUS-CPN effectively with no differences in terms of complications between the techniques,but more studies are needed. The effect of EUS-CPN on pain improvement, patient survival and patient quality of life should be evaluated in well-designed randomized clinical trials. Further research also needs to be performed to clarify the best time frame in performing a EUS-CPN.     

Efficacy of Preoperative Radiation Therapy for Resectable Rectal Adenocarcinoma When Combined With Oral Tegafur-Uracil Modulated With Leucovorin

PURPOSE: The aim of this study was to evaluate the efficacy of preoperative radiation therapy for resectable rectal adenocarcinoma (T3-T4) when delivered in combination with chemotherapy (oral tegafur-uracil modulated with leucovorin). METHODS: Thirty-eight patients (23 males; mean age, 62 years.) with histologically proven rectal adenocarcinoma with primary tumor clinical classification T3-T4 (resectable) and N0 or N1-N2, according to TNM staging system, took part in the present clinical trial. After tumor and metastasis resectability confirmation, radiation therapy was administered by delivering a dose of 45 Gy in 25 fractions for 5 weeks. Chemotherapy treatment was initiated on the same day as radiotherapy and consisted of intravenous infusion of 6S-steroisomer of leucovorin 250 mg/m2/day in 2 hours on Day 1, followed by oral 350 or 300 mg/m2/day of tegafur (a 5-fluorouracil prodrug) plus uracil on Days 1 to 14 divided into 2 daily doses, and oral 6S-steroisomer of leucovorin 7.5 mg/12 hours on Days 2 to 14, with a total of 102 courses of neoadjuvant chemotherapy (i.e., mean of 2.7 courses per patient). Six additional courses of tegafur-uracil were given postoperatively to all 38 patients but 1 who refused. RESULTS: As a result of preoperative chemoradiation treatment, 4 (10.5 percent) complete responses, 20 (52.6 percent) partial responses, and 14 (36.8 percent) patients with disease stabilization were observed. No patients had preoperative disease progression. Histologically proven downstaging was observed in 23 (60 percent) patients. On initial evaluation, only 39 percent of patients were considered as being good candidates for sphincter-preserving surgery; however, on preoperative chemoradiation completion this figure increased up to 60 percent. For the 23 patients eventually undergoing sphincter-preserving surgery, postoperative sphincter function assessment showed excellent function in 15 (65 percent) patients, good in 5 (22 percent), fair in 2 (9 percent), and poor in 1(4 percent). With a median follow-up of 37 (range, 10–62) months, local failure was found in 3 (8 percent) patients and distant failure in 2 (5 percent). Three-year actuarial disease-free survival and 3-year overall survival rates were 83 and 90 percent, respectively. Local control rate was 92 percent. Toxicity and postoperative complication rates were reasonable. CONCLUSIONS: Our neoadjuvant radiation therapy protocol is efficient for the preoperative treatment of resectable rectal adenocarcinoma when combined with chemotherapy (oral tegafur-uracil modulated with leucovorin). However, this protocol needs to be tested in a phase-III clinical trial with a larger sample size.     

Familial hypercholesterolemia in Spain: case-finding program, clinical and genetic aspects

A case-finding program for the identification of patients with familial hypercholesterolemia (FH) has been established in Spain. The program is based on family investigation and molecular genetic testing for mutations in the low-density lipoprotein receptor gene. To assist this program, intensive research into the molecular basis of FH and genotype/phenotype relations is performed. To optimize DNA testing, a DNA-diagnostic platform has been constructed that is composed of systematic mutation screening by single-strand conformation polymorphism (SSCP) analysis, DNA-sequencing, Southern blotting, and the use of microarrays for high-throughput analysis. To date, 161 different mutations leading to inherited hypercholesterolemia have been identified in Spanish patients with FH. In addition, a patient organization was founded to ensure patient support and follow-up. To further facilitate FH case-finding and patient follow-up, we initiated the publication of a set of guidelines for diagnosis and clinical management of FH that can be applied internationally.     

A comparison of the validity of two indirect utility instruments as measures of postoperative recovery

Background

Cost-effectiveness analyses of surgical interventions require valid measures of postoperative recovery. The objective of this study was to compare the validity of two indirect utility instruments, the Short Form 6D (SF-6D) and EuroQol 5D (EQ-5D), as measures of postoperative recovery.

Materials and methods

A prospective cohort of patients undergoing elective colorectal resection at two university-affiliated institutions from October 2012–October 2013 completed the SF-6D and EQ-5D (including the EQ-visual analog scale [EQ-VAS]) at baseline (before surgery), and at 4 and 8 wk after surgery. Responsiveness and construct validity were assessed through a priori hypotheses.

Results

A total of 165 patients were included. The SF-6D was the most responsive to the expected postoperative changes at 4 and 8 wk compared with the EQ-5D and the EQ-VAS. The 4-wk SF-6D, EQ-5D, and EQ-VAS discriminated between patients with and without complications after controlling for confounders with adjusted mean differences of −0.070 (95% confidence interval [CI] −0.126 to −0.015), −0.133 (95% CI −0.231, −0.030), and −7.91 (95% CI −14.77, −1.04), respectively. Mean SF-6D and EQ-5D values were significantly different from the US population norms at all time points, but the magnitude of change was highest for the SF-6D. The strength of correlation between all three instruments was moderate at all time points (r = 0.550–0.684, all P < 0.05).

Conclusions

The SF-6D preference-based health index appears to be a more valid measure of postoperative recovery than the EQ-5D and EQ-VAS in surgical cost-effectiveness analyses.